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Greco was born in Ciaculli, a town in the province of Palermo. His father was another hitman nicknamed "Scarpa", an Italian word meaning "shoe". As such, Greco would be given a nickname based on his father's: "Scarpuzzedda", meaning "little shoe". At school, Greco was considered a talented student by his teachers and peers, for his extreme knowledge of the Latin and Greek languages. Greco eventually joined the Sicilian Mafia and became a high-ranking member of the Sicilian Mafia. He was one of the leaders of the Sicilian Mafia Commission, which was ruled by his uncle Michele Greco, a.k.a. "The Pope". Michele was the boss of the Ciaculli, who were allied with the Corleonesi and their bosses, Salvatore Riina and Bernardo Provenzano.

For three years, Greco murdered dozens of people during the Second Mafia War. On one occasion, Greco brutally tortured a fifteen-year-old boy and chopped his arm off before shooting him in the head, because he had vowed to avenge his father, who was previously murdered by Greco. In July 1981, Greco attempted to assassinate a man named Salvatore Contorno, but failed and was shot by him in the chest, though a bulletproof vest saved his life. Greco also helped many other criminals in their killings. One of these criminals was the boss of the Corso de Mille neighborhood in Palermo, Filippo Marchese, who would bring his victims to a shack he nicknamed the "Room of Death", located in a wasteland far away from the city, where he would torture and kill them. Greco would participate in some of the torture and murder sessions, for no reason other than the thrill of it. In November 1982, Greco and Marchese invited another member of the Sicilian Mafia, Rosario Riccobono, and eight of his men to a barbecue at Michele Greco's state. Riccobono was personally strangled by Greco, and his men were massacred by Greco and Marchese's men. After killing Riccobono, Greco proceeded to murder even more of his men and his entire family, simply because Riccobono was not "useful" anymore for the Sicilian Mafia. Ironically, Greco's next victim would be Marchese himself, after Riina had ordered his death.

At that point, Greco was considered the underboss of the Ciaculli. Despite this, Greco continued to murder his targets by himself without the assistance of others. On July 29, 1983, Greco detonated a car bomb that killed Rocco Chinnici and three other people. With the end of the Second Mafia War, Greco began to act as the actual boss of the Ciaculli family, while his uncle went into hiding. In order to reduce the strength of the Ciaculli family and Greco's position, Riina ordered the massacre of Piazza Scaffa, resulting in the death of eight people in the Ciaculli mandamento. The event showed Greco's lack of effective power over his own territory. On August 6, 1985, Greco and his hit-squad ambushed and shot a police investigator named Antonino Cassarà. The attack resulted not only in the assassination of Cassarà himself, but one of his bodyguards as well; another bodyguard was severely injured but survived the attack. A month later, Riina ordered his death and Greco was murdered in his own home by two fellow hitmen, who shot him to death. Shortly after his death, Riina explained why he killed Greco to one of Greco's close friends, saying, "You know we've found the medicine for madmen? ...We've killed 'Little Shoe'; he'd become crazy."

Though Greco's mostly killed his victims during contract killings, he also took delight in torturing and murdering random people when he had the chance, for no apparent reason other than the thrill of it, and also assassinating ex-Mafia members and police officers, again for no reason. After killing his targets, he would also kill their families. Greco had a variety of ways to kill his victims, though he stated that shooting them with an AK-47 assault rifle was his favorite method. He also strangled, garroted, hacked, stabbed, bludgeoned, and bombed victims. Greco had his own squad of hitmen, who would rarely kill his targets for him, but often worked together with their boss. In order to dispose of his victims' bodies, Greco would throw them into acid vats or give them to pigs for consumption. Though he rarely committed himself to it, Greco also participated in acts of terrorism to maintain his power and position.

Greco served as inspiration for prolific serial killer and hitman Giuseppe Montolo. Both were Italian hitmen who shared the same first name, survived a gunshot wound during an attempt on their life, were deeply involved in criminal syndicates through family connections, and were later murdered by fellow hitmen.